Mita Tsuneyuki, Furukawa-Hibi Yoko, Takeuchi Hideyuki, Hattori Hisashi, Yamada Kiyofumi, Hibi Hideharu, Ueda Minoru, Yamamoto Akihito
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Behav Brain Res. 2015 Oct 15;293:189-97. doi: 10.1016/j.bbr.2015.07.043. Epub 2015 Jul 22.
Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by a decline in cognitive abilities and the appearance of β-amyloid plaques in the brain. Although the pathogenic mechanisms associated with AD are not fully understood, activated microglia releasing various neurotoxic factors, including pro-inflammatory cytokines and oxidative stress mediators, appear to play major roles. Here, we investigated the therapeutic benefits of a serum-free conditioned medium (CM) derived from the stem cells of human exfoliated deciduous teeth (SHEDs) in a mouse model of AD. The intranasal administration of SHEDs in these mice resulted in substantially improved cognitive function. SHED-CM contained factors involved in multiple neuroregenerative mechanisms, such as neuroprotection, axonal elongation, neurotransmission, the suppression of inflammation, and microglial regulation. Notably, SHED-CM attenuated the pro-inflammatory responses induced by β-amyloid plaques, and generated an anti-inflammatory/tissue-regenerating environment, which was accompanied by the induction of anti-inflammatory M2-like microglia. Our data suggest that SHED-CM may provide significant therapeutic benefits for AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是认知能力下降以及大脑中出现β-淀粉样蛋白斑块。尽管与AD相关的致病机制尚未完全明确，但激活的小胶质细胞释放包括促炎细胞因子和氧化应激介质在内的各种神经毒性因子似乎起主要作用。在此，我们在AD小鼠模型中研究了源自人脱落乳牙干细胞（SHEDs）的无血清条件培养基（CM）的治疗益处。在这些小鼠中鼻内给予SHEDs可显著改善认知功能。SHED-CM含有参与多种神经再生机制的因子，如神经保护、轴突伸长、神经传递、炎症抑制和小胶质细胞调节。值得注意的是，SHED-CM减弱了β-淀粉样蛋白斑块诱导的促炎反应，并产生了抗炎/组织再生环境，同时伴有抗炎性M2样小胶质细胞的诱导。我们的数据表明，SHED-CM可能为AD提供显著的治疗益处。
